Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells

Abstract

Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95% was achieved by depositing an intracellular total thermal energy with about 50% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65% after MNP were internalized inside cells.

Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance

“…As a result of these three mechanisms, SPION and magnetic temperature gradually increase in an AFM until a saturation temperature is achieved [37,38]. In a cellular environment, however, SPION are immobilized inside lysosomes and form agglomerates [39,40]. This leads to partial blocking of the above-mentioned Brownian relaxation and to a drop in heating efficiency.…”

Magnetic Hyperthermia for Cancer Treatment: Main Parameters Affecting the Outcome of In Vitro and In Vivo Studies

“…The IT administration of MNPs seems to be generally considered a more invasive procedure than the IV counterpart and it is known to result in uneven distribution of the MNPs in the tumor, which can lead to a significant temperature difference across the tumor [ 76 ]. This can be minimized by multiple site IT injection [ 77 ] or by magnetic targeting of MNPs after IV injection, i.e., using an external magnet to concentrate the MNPs in the area of interest [ 76 , 78 ]. Magnetic targeting, combined with antibody targeting and the EPR effect, have been reported to allow the tumor to be specifically heated [ 60 ].…”

“…Magnetic targeting, combined with antibody targeting and the EPR effect, have been reported to allow the tumor to be specifically heated [ 60 ]. Among the advantages of IT administration of MNPs are the less complex formulation usually required and that, in general, it results more effectively than the IV route [ 78 ]. Additionally, it opens the possibility to treat tumors where MNPs do not accumulate to sufficient amounts after IV injection.…”

The Potential Biomedical Application of NiCu Magnetic Nanoparticles

“…In addition to the abovementioned investigations, research studies from the last couple of years showed that NiCu MNPs have great potential in several other types of biomedical applications, such as their use in bimodal cancer treatments that combine MH and controlled drug delivery [47][48][49]. Nevertheless, another important factor to be considered when applying a novel formulation for MH is the overall concentration of the respective NPs at the tumor site [50,51]. Specifically, NPs with a low specific loss power (SLP) need to be more concentrated in the tumor, with the consequent disadvantages of bioaccumulation and long-term toxicity [52,53].…”